Estrogen Receptor/ERR Degrader

ZN-c5 is a selective and orally active estrogen receptor degrader. ZN-c5 exhibits high potency in the cellular assay (MCF-7, IC₅₀ = 0.3 nM) and binds with high affinity to ERα and ERβ (IC₅₀ = 0.4 nM and 0.8 nM, respectively). ZN-c5 inhibits tumor growth in MCF-7 mouse xenograft model and WHIM20 xenograft model. ZN-c5 can be used for the study of breast cancer.

Giredestrant tartrate (GDC-9545 tartrate) is an orally active, full, selective Estrogen receptor α (ERα) degrader and antagonist with a DC₅₀ of 0.03 nM. Giredestrant tartrate promotes the degradation of ERα protein, including the ESR1^Y537S mutant ERα. Giredestrant tartrate reduces uterine wet weight in immature rats and induces a low cuboidal phenotype in their endometrial epithelium. Giredestrant tartrate induces tumor regression in both ESR1^Y537S mutant and wild-type ERα tumor models. Giredestrant tartrate can be used for the research of ER⁺ breast cancer.

PVTX-321 (Compound 16a) is an orally active estrogen receptor α (ERα) degrader. PVTX-321 can potently degrade ERα (DC₅₀=0.15 nM in MCF-7 cells) and also has inhibitory activity against mutant ERα (IC₅₀=59 nM). PVTX-321 is promising for research of ER+/HER2- breast cancer.

ERα degrader 8 (Compound 18j) is a selective Estrogen Receptor degrader. ERα degrader 8 is degrader to MCF-7 cells with IC₅₀ value of 0.15 μM.

THIQ-40 is a tetrahydroisoquinoline-based, orally active, and selective estrogen receptor ERα degrader (SERD) (IC₅₀=17 nM), with antitumor efficacy. THIQ-40 possesses functional ERα antagonistic activity, promotes ERα degradation and forms stable ERαLBD complexes. THIQ-40 shows the characteristic of rapid racemization in multi-species plasma. THIQ-40 can be widely applied to studies on the relevant mechanisms and drug development of ERα-positive breast cancer.

PROTAC ERα Degrader-13 is an orally active PROTAC molecule that efficiently and selectively degrades ERα (DC₅₀ = 3.78 nM). PROTAC ERα Degrader-13 has the characteristics of strong anti proliferation (IC₅₀ = 0.6 nM), induction of apoptosis, and overcoming drug resistance in MCF-7 cells. PROTAC ERα Degrader-13 has good safety and no significant organ toxicity. PROTAC ERα Degrader-13 can be used for cancer research.

NCP07 is a PROTAC degrader targeting the coactivator-binding site (CBS) of ERα. NCP07 induces the formation of the ERα-NCP07-VHL ternary complex and promotes ERα degradation via the ubiquitin-proteasome system. NCP07 induces apoptosis and cell cycle arrest in endocrine therapy-resistant breast cancer cells. NCP07 inhibits the proliferation of wild-type and ESR1-mutant breast cancer cells. NCP07 is applicable to breast cancer-related research.

OBHSA is a selective estrogen receptor (ERα) degrader. OBHSA blocks the cell cycle by degrading cyclin D1, thereby overcoming Tamoxifen (HY-13757A) resistance. OBHSA also triggers excessive activation of the unfolded protein response (UPR) by inducing an increase in intracellular reactive oxygen species, ultimately leading to cell apoptosis. In addition, OBHSA can also be used as an ERα ligand to synthesize PROTAC degraders.

ERα degrader 11 (compound B16) is a selective ERα degrader that can be used as an estrogen receptor probe to investigate ER status in ER-positive breast cancer cells.

ERα degrader 12 (Compound RA3) is an estrogen receptor α (ERα) degrader with antitumor properties. ERα degrader 12 induces pronounced tumor growth inhibition in a breast cancer xenograft mouse model.

F0840-0093 is a highly selective estrogen receptor α (ERα) degrader. F0840-0093 exhibits potent antiproliferative activity against T47D cells with an IC₅₀ value of 4.65 μM. F0840-0093 is promising for research of estrogen receptor-positive (ER+) breast cancer.

ERD-12310A is an orally active ERα PROTAC degrader, with a K_i value of 0.95 nM against human ERα and a DC₅₀ of 47 pM for ERα in MCF-7 cells. ERD-12310A forms a ternary complex with ERα and the CRBN E3 ubiquitin ligase, thereby inducing ubiquitination and proteasomal degradation of wild-type and ESR1^Y537S mutant ERα. ERD-12310A induces tumor regression in ER+ breast cancer xenografts and inhibits tumor growth in ESR1^Y537S mutant breast cancer xenografts. ERD-12310A can be used in studies related to ER-positive breast cancer and ESR1-mutant breast cancer.

GNE-5472 is a potent bifunctional ERα PRRTAC degrader, with its E3 ligand being a pan-IAP antagonist. GNE-5472 antagonizes cIAP1/2, activating the non-classical NF-κB pathway, resulting in a significant upregulation of TNFα expression. GNE-5472 inhibits the proliferation of breast cancer cells and induces cell apoptosis. GNE-5472 can be used for the study of breast cancer.

Elacestrant-d₁₀ is the deuterium labeled of Elacestrant (HY-19822). Elacestrant is an orally available and selective estrogen receptor degrader (SERD) with IC₅₀s of 48 and 870 nM for ERα and ERβ, respectively. Elacestrant also inhibits growth of ER⁺ breast cancer cell lines in vitro and in vivo.

PROTAC ERα Degrader-8 (compound ii-56) is a potent PROTAC degrader of Erα, with DC₅₀ of 0.000006 μM in MCF7 cells.

PROTAC ERα Degrader-12 is a VHL-recruiting ERα PROTAC degrader with a DC₅₀ of 1.02 μM in MCF-7 cells. PROTAC ERα Degrader-12 binds to ERα and recruits the VHL E3 ligase to form a ternary complex, promoting proteasomal degradation of both wild-type and mutant ERα, thereby inhibiting ER-mediated transcriptional activity and breast cancer cell proliferation. PROTAC ERα Degrader-12 can be used in the research of ERα-positive breast cancer.

X15695 is selective and orally active estrogen receptor (ERα) degrader. X15695 is an aryl hydrocarbon receptor (AHR) ligand. X15695 enables AHR to form a complex with the ERα, promoting its proteasomal degradation. X15695 inhibits the breast cancer cells proliferation, promotes cell cycle block and induces apoptosis. X15695 can be used for the study of breast cancer.

ER degrader 12 (Example 1) is an estrogen receptor (ER) degrader with IC₅₀ values for ERα and ERβ of 2.3 and 80.2 nM respectively (TR-FRET experiment). ER degrader 12 inhibits the proliferation of MCF-7 cells, with an IC₅₀ of 1.53 nM. ER degrader 12 can be used for research on breast cancer.

PROTAC ER Degrader-15 (Compound 40) is an orally active degrader of the estrogen receptor (ER) with anticancer activity，which can be used in breast cancer research (Pink: Target Protein Ligand (HY-170334); Black: Linker (HY-30756); Blue: E3 Ligase Ligand (HY-138793); E3 Ligase Ligand-Linker Conjugate (HY-169979)).

PROTAC ER Degrader-16 is an orally active ERα PROTAC degrader with a DC₅₀ of 1.4 nM and an IC₅₀ of 1.9 nM. PROTAC ER Degrader-16 inhibits ER-dependent breast cancer cell proliferation and exerts anti-tumor effects in mouse models. PROTAC ER Degrader-16 can be used for breast cancer research.